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The role of the obestatin/GPR39 system in human gastric adenocarcinomas

2015; Impact Journals LLC; Volume: 7; Issue: 5 Linguagem: Inglês

10.18632/oncotarget.6718

1949-2553

Begoña Otero‐Alén, Saúl Leal‐López, María Otero Alén, Patricia Viaño, Victoria García-Castro, Carlos S. Mosteiro, A. Beiras, Felipe F. Casanueva, Rosalı́a Gallego, Tomás García‐Caballero, Jesús P. Camiña, Yolanda Pazos,

Growth Hormone and Insulin-like Growth Factors

// Begoña O. Alén 1, 2 , Saúl Leal-López 1, 2 , María Otero Alén 3, 4 , Patricia Viaño 3, 4 , Victoria García-Castro 4 , Carlos S. Mosteiro 1, 2 , Andrés Beiras 3, 4, 5 , Felipe F. Casanueva 1, 2, 6 , Rosalía Gallego 2, 3, 5 , Tomás García-Caballero 3, 4, 5 , Jesús P. Camiña 1, 2 , Yolanda Pazos 1, 2 1 Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Spain 2 CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain 3 IDIS, CHUS, Santiago de Compostela, Spain 4 Servicio de Anatomía Patológica, CHUS, SERGAS, Santiago de Compostela, Spain 5 Departamento de Ciencias Morfológicas, Universidad de Santiago de Compostela (USC), Santiago de Compostela, Spain 6 Departamento de Medicina, USC, Santiago de Compostela, Spain Correspondence to: Yolanda Pazos, e-mail: yolanda.pazos.randulfe@sergas.es Keywords: GPR39, obestatin, stomach, adenocarcinoma Received: July 29, 2015 Accepted: November 25, 2015 Published: December 22, 2015 ABSTRACT Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer.